The isolated canine brain preparation will be used to study the following: (A) Unidirectional flux of (1) norepinephrine and 5- hydroxytryptamine, (2) D-leucine, (3) glucose during anoxia, (4) long chain fatty acids and (5) Pyruvate and acetate using an indicator dilution technique with Na22 as the intervascular indicator. (B) Brain glucose metabolism during perfusion with blood having either an elevated CO2 tension (PCO2 60 mm Hg) or a depressed oxygen tension (PO2 25 mm Hg). (C) The incorporation of L-leucine and ketone bodies from blood into brain carbon dioxide, amino acids, proteins, lipids. (D) The influence of high O2 and low CO2 tension on cerebral vascular tension. (E) Patterns of cerebral blood flow in brains perfused at high arterial pressure or low oxygen tension coupled with microscopic examination of areas observed to be underperfused.